PMID- 16947022
OWN - NLM
STAT- MEDLINE
DCOM- 20070605
LR  - 20240427
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 56
IP  - 5
DP  - 2007 May
TI  - Induction of apoptosis and immune response by all-trans retinoic acid plus 
      interferon-gamma in human malignant glioblastoma T98G and U87MG cells.
PG  - 615-25
AB  - Glioblastoma is the most common and highly malignant brain tumor. It is also one 
      among the most therapy-resistant human neoplasias. Patients die within a year of 
      diagnosis despite the use of available treatment strategies such as surgery, 
      radiotherapy, and chemotherapy. Thus, there is a critical need to find a novel 
      therapeutic strategy for treating this disease. Here, we have investigated the 
      molecular mechanisms for induction of apoptosis as well as for activation of 
      immune components in human malignant glioblastoma T98G and U87MG cells following 
      treatment with all-trans retinoic acid (ATRA) plus interferon-gamma (IFN-gamma). 
      Treatment of glioblastoma cells with ATRA alone prevented cell proliferation and 
      induced astrocytic differentiation, while IFN-gamma alone induced apoptosis and 
      modulated expression of human leukocyte antigen (HLA) class II molecules such as 
      HLA-DRalpha, HLA-DR complex, invariant chain (Ii), HLA-DM (an important catalyst 
      of the class II-peptide loading), and gamma interferon-inducible lysosomal 
      thiol-reductase (GILT). Interestingly, both T98G and U87MG cells showed more 
      increase in apoptosis with expression of the HLA class II components for an 
      effective immune response following treatment with ATRA plus IFN-gamma than with 
      IFN-gamma alone. Apoptotic mode of cell death was confirmed morphologically by 
      Wright staining and biochemically by measuring an increase in caspase-3 activity. 
      While conversion of tumor cells into HLA class II+/Ii- cells by stimulation with 
      the helper CD4+ T cells is thought to be challenging, this study reports for the 
      first time that treatment of glioblastoma cells with ATRA plus IFN-gamma can 
      simultaneously enhance apoptosis and expression of the HLA class II immune 
      components with a marked suppression of Ii expression. Taken together, this study 
      suggests that induction of apoptosis and immune components of the HLA class II 
      pathway by ATRA plus IFN-gamma may be a promising chemoimmunotherapeutic strategy 
      for treatment of human malignant glioblastoma.
FAU - Haque, Azizul
AU  - Haque A
AD  - Department of Microbiology and Immunology, Medical University of South Carolina, 
      Charleston, SC 29425, USA.
FAU - Das, Arabinda
AU  - Das A
FAU - Hajiaghamohseni, Laela M
AU  - Hajiaghamohseni LM
FAU - Younger, Austin
AU  - Younger A
FAU - Banik, Naren L
AU  - Banik NL
FAU - Ray, Swapan K
AU  - Ray SK
LA  - eng
GR  - R01 NS031622/NS/NINDS NIH HHS/United States
GR  - CA-91460/CA/NCI NIH HHS/United States
GR  - R01 NS057811/NS/NINDS NIH HHS/United States
GR  - NS-57811/NS/NINDS NIH HHS/United States
GR  - NS-31622/NS/NINDS NIH HHS/United States
GR  - R01 CA091460/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060901
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 5688UTC01R (Tretinoin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/*drug effects/immunology
MH  - Brain Neoplasms/*immunology/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Glioblastoma/*immunology/metabolism/pathology
MH  - Histocompatibility Antigens Class II/drug effects
MH  - Humans
MH  - Interferon-gamma/administration & dosage
MH  - Tretinoin/administration & dosage
PMC - PMC11030588
EDAT- 2006/09/02 09:00
MHDA- 2007/06/06 09:00
PMCR- 2006/09/01
CRDT- 2006/09/02 09:00
PHST- 2006/05/12 00:00 [received]
PHST- 2006/07/24 00:00 [accepted]
PHST- 2006/09/02 09:00 [pubmed]
PHST- 2007/06/06 09:00 [medline]
PHST- 2006/09/02 09:00 [entrez]
PHST- 2006/09/01 00:00 [pmc-release]
AID - 219 [pii]
AID - 10.1007/s00262-006-0219-6 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2007 May;56(5):615-25. doi: 10.1007/s00262-006-0219-6. 
      Epub 2006 Sep 1.